Agomab's Ontunisertib in Fibrostenosing Crohn's Disease: Phase 2a Results and Future Implications

Agomab reports positive Phase 2a topline data for ontunisertib in fibrostenosing Crohn’s disease, suggesting a tolerable, gut‑restricted ALK5 inhibition strategy that could provide an oral option combining anti‑inflammatory and anti‑fibrotic effects for symptomatic ileal strictures.

The company treated 103 randomized participants over a 12‑week double‑blind period and assessed safety, pharmacokinetics, and exploratory endoscopic and imaging measures.

Safety analyses showed similar incidence and severity of adverse events across active and placebo arms, with no treatment‑related cardiac toxicity or overt pro‑inflammatory laboratory or clinical signals. Pharmacokinetic data reported high local gastrointestinal exposure with limited systemic circulation—supporting a gut‑restricted therapeutic index for ontunisertib—and initial open‑label extension observations are consistent with the blinded findings. The lack of untoward laboratory trends or signal amplification in patients already receiving advanced biologic therapy reduces immediate safety concerns and supports continued clinical development.

Per the announcement, the sponsor reported exploratory trends toward improvement in some SES‑CD components and directional shifts in multiple MRE parameters relevant to strictures; these company‑reported signals were consistent across endoscopic and imaging readouts and align with the proposed dual anti‑inflammatory/anti‑fibrotic mechanism of ALK5 inhibition. These endpoints were exploratory—the study was not powered to confirm efficacy—so the observed trends are hypothesis‑generating and justify a larger, controlled follow‑up study.

Agomab has signaled plans to initiate a Phase 2b program while preparing detailed STENOVA datasets for scientific presentation and engaging regulatory authorities on the development pathway. The sponsor intends to use target‑engagement and transcriptomic biomarker data to refine dose selection and patient enrichment strategies in subsequent studies.